2007 Grant - S. Lee

Quantitative in Vivo Measure of an Alzheimer's Disease Drug Treatment in Transgenic Mice

2007 New Investigator Research Grant

Two characteristic features of Alzheimer pathology are amyloid plaques and neurofibrillary tangles. Neurofibrillary tangles occur inside of nerve cells and involve the abnormal behavior of a protein called tau (tau pathology). Tau is a component of microtubules, structures inside of nerve cells that are important for the transport of nutrients along the cell's long processes (axons). Tau pathology leads to disruption of microtubules and subsequent disruption of nutrient transport inside of nerve cells.

Researchers have sought to develop drugs that can stabilize microtubules in the hopes that such drugs would prevent tau pathology. Sang-Pil Lee, Ph.D., is part of a collaborative group of researchers, some of whom have developed a drug that is able to penetrate the brain and stabilize microtubules. Dr. Lee and colleagues have developed a technique that allows them to visualize tau pathology using magnetic resonance imaging (MRI). They plan to use this technique to test the effectiveness of the new drug, which is related to the anticancer drug taxol, in living mice.

The researchers will use mice that have been genetically altered to express both amyloid plaque and tau pathology. The researchers will study how tau pathology disrupts nutrient transport in nerve cells, and whether the new drug prevents or slows the development of tau pathology. These studies may provide important clues into how tau pathology and amyloid plaques are related, and they may provide initial information about the efficacy of a new treatment approach for Alzheimer pathology.